Experience (Mostly Negative) with the Use of Sympathomimetic Agents for Weight Loss

Sympathomimetic agents have a poor history of long-term success in the treatment of obesity. From earlier experiences with amphetamine and its analogs, to more recent drugs with direct effects on adrenergic receptors or indirect effects from release of catecholamines or inhibition of reuptake, cardiovascular toxicity (strokes and cardiac arrhythmias) has been the major concern. These concerns also extended to food supplements containing ephedra alkaloids and may require consideration for current supplements containing the sympathomimetic drug, synephrine

Anti-Tumor Activity of Phenoxybenzamine and Its Inhibition of Histone Deacetylases

The principal finding from this study was the recognition that the α-adrenergic antagonist, phenoxybenzamine, possesses histone deacetylase inhibitory activity. Phenoxybenzamine is approved by the United States Food and Drug Administration for the treatment of hypertensive crises associated with tumors of the adrenal medulla, pheochromocytomas. It has several off label indications relative to its capacity to relax vascular smooth muscle and smooth muscle of the urogenital tract. The drug also has a long history of apparent efficacy in ameliorating, and perhaps reversing, the severe symptoms of neuropathic pain syndromes. Our interest in this feature of the drug relates to the fact that certain types of neuropathic pain, in particular complex regional pain syndrome, demonstrate a proliferative nature, with the capacity to spread from an injured limb, for example, to a non-injured limb and perhaps to essentially the entire body. Sensory neuronal sprouting in the spinal cord has been observed under conditions where there is a high sensory input from painful stimuli. Searches of gene expression signatures in the BroadBuild02 Molecular Signature Database using their connectivity map software suggested that phenoxybenzamine may have histone deacetylase inhibitory activity. Studies by others have reported inhibitory effects of phenoxybenzamine on growth, invasion and migration of human tumor cell cultures and, in one study, inhibition of tumor expansion in animal experiments. Inhibitory effects on human tumor cell cultures are also reported in the present study. Phenoxybenzamine was also found to have histone deacetylase inhibitory activity; histone deacetylase isoforms 5, 6, and 9 were the most sensitive to inhibition by phenoxybenzamine. The importance of elevated levels of these isoforms as biomarkers of poor prognosis in human malignant disease, and the recognized suppression of tumor growth that may accrue from their inhibition, opens consideration of possible translation of phenoxybenzamine to new clinical applications. This might be facilitated by the fact that phenoxybenzamine is already an approved drug entity. There appears to be no previous report of the activity of phenoxybenzamine as a histone deacetylase inhibitor

Evaluation of bistable systems versus matched filters in detecting bipolar pulse signals

This paper presents a thorough evaluation of a bistable system versus a matched filter in detecting bipolar pulse signals. The detectability of the bistable system can be optimized by adding noise, i.e. the stochastic resonance (SR) phenomenon. This SR effect is also demonstrated by approximate statistical detection theory of the bistable system and corresponding numerical simulations. Furthermore, the performance comparison results between the bistable system and the matched filter show that (a) the bistable system is more robust than the matched filter in detecting signals with disturbed pulse rates, and (b) the bistable system approaches the performance of the matched filter in detecting unknown arrival times of received signals, with an especially better computational efficiency. These significant results verify the potential applicability of the bistable system in signal detection field.Comment: 15 pages, 9 figures, MikTex v2.

Coherent Signal Amplification in Bistable Nanomechanical Oscillators by Stochastic Resonance

Stochastic resonance is a counter-intuitive concept[1,2], ; the addition of noise to a noisy system induces coherent amplification of its response. First suggested as a mechanism for the cyclic recurrence of ice ages, stochastic resonance has been seen in a wide variety of macroscopic physical systems: bistable ring lasers[3], SQUIDs[4,5], magnetoelastic ribbons[6], and neurophysiological systems such as the receptors in crickets[7] and crayfish[8]. Although it is fundamentally important as a mechanism of coherent signal amplification, stochastic resonance is yet to be observed in nanoscale systems. Here we report the observation of stochastic resonance in bistable nanomechanical silicon oscillators, which can play an important role in the realization of controllable high-speed nanomechanical memory cells. Our nanomechanical systems were excited into a dynamic bistable state and modulated in order to induce controllable switching; the addition of white noise showed a marked amplification of the signal strength. Stochastic resonance in nanomechanical systems paves the way for exploring macroscopic quantum coherence and tunneling, and controlling nanoscale quantum systems for their eventual use as robust quantum logic devices.Comment: 18 pages, 4 figure

Review Article Phenoxybenzamine in Complex Regional Pain Syndrome: Potential Role and Novel Mechanisms

There is a relatively long history of the use of the -adrenergic antagonist, phenoxybenzamine, for the treatment of complex regional pain syndrome (CRPS). One form of this syndrome, CRPS I, was originally termed reflex sympathetic dystrophy (RSD) because of an apparent dysregulation of the sympathetic nervous system in the region of an extremity that had been subjected to an injury or surgical procedure. The syndrome develops in the absence of any apparent continuation of the inciting trauma. Hallmarks of the condition are allodynia (pain perceived from a nonpainful stimulus) and hyperalgesia (exaggerated pain response to a painful stimulus). In addition to severe, unremitting burning pain, the affected limb is typically warm and edematous in the early weeks after trauma but then progresses to a primarily cold, dry limb in later weeks and months. The later stages are frequently characterized by changes to skin texture and nail deformities, hypertrichosis, muscle atrophy, and bone demineralization. Earlier treatments of CRPS syndromes were primarily focused on blocking sympathetic outflow to an affected extremity. The use of anadrenergic antagonist such as phenoxybenzamine followed from this perspective. However, the current consensus on the etiology of CRPS favors an interpretation of the symptomatology as an evidence of decreased sympathetic activity to the injured limb and a resulting upregulation of adrenergic sensitivity. The clinical use of phenoxybenzamine for the treatment of CRPS is reviewed, and mechanisms of action that include potential immunomodulatory/anti-inflammatory effects are presented. Also, a recent study identified phenoxybenzamine as a potential intervention for pain mediation from its effects on gene expression in human cell lines; on this basis, it was tested and found to be capable of reducing pain behavior in a classical animal model of chronic pain

Anesthesiologists\u27 Preferences regarding Visitor Presence during Placement of Neuraxial Labor Analgesia

Introduction: Neuraxial labor analgesia has become an integral part of modern obstetric anesthetic practice. Presence of a familiar person during its placement may be beneficial to the patient. A survey was sent to anesthesiologists practicing obstetric anesthesia in the USA to determine their views. Methods: The survey queried the following: existence of a written policy; would they allow a visitor; visitor\u27s view, sitting or standing; reasons to allow or not allow a visitor; and influence by other staff on the decision. The responses were analyzed using multiple chi-square analyses. Results: Most practitioners supported allowing a visitor during placement. Reduction of patient anxiety and fulfillment of patient request were the major reasons for allowing a visitor. Sitting position and no view of the workspace were preferred. Visitor interference and safety were cited as the major reasons for precluding a visitor. Nonanesthesia providers rarely influenced the decision. Epidural analgesia was the preferred technique. Essentially no bias was found in the responses; there was statistical uniformity regardless of procedures done per week, years in practice, professional certification, geographic region (rural, urban, or suburban), or academic, private, or government responders. Conclusion: The practice of visitor presence during the placement of neuraxial labor analgesia is gaining acceptance

Resonance phenomena in discrete systems with bichromatic input signal

We undertake a detailed numerical study of the twin phenomena of stochastic and vibrational resonance in a discrete model system in the presence of bichromatic input signal. A two parameter cubic map is used as the model that combines the features of both bistable and threshold settings. Our analysis brings out several interesting results, such as, the existence of a cross over behaviour from vibrational to stochastic resonance and the possibility of using stochastic resonance as a filter for the selective detection/transmission of the component frequencies in a composite signal. The study also reveals a fundamental difference between the bistable and threshold mechanisms with respect to amplification of a multi signal input.Comment: 17 pages, 16 figures, submitted to European Physical Journa

Stochastic synchronization in globally coupled phase oscillators

Cooperative effects of periodic force and noise in globally Cooperative effects of periodic force and noise in globally coupled systems are studied using a nonlinear diffusion equation for the number density. The amplitude of the order parameter oscillation is enhanced in an intermediate range of noise strength for a globally coupled bistable system, and the order parameter oscillation is entrained to the external periodic force in an intermediate range of noise strength. These enhancement phenomena of the response of the order parameter in the deterministic equations are interpreted as stochastic resonance and stochastic synchronization in globally coupled systems.Comment: 5 figure

Intraoperative Blood Loss During Induced Abortion: A Comparison of Anesthetics

Objective: To determine whether there is a difference in intraoperative bleeding with inhalational versus noninhalational anesthetic agents for patients undergoing suction dilatation and curettage for first-trimester induced abortion. Methods: This is an IRB-approved retrospective chart review of the electronic medical records of patients undergoing induced abortion at gestational ages between 5 0/7 and 14 0/7 weeks of pregnancy at the New York City Health + Hospitals/Metropolitan. The records of 138 patients who underwent suction dilatation and curettage for induced abortion between June 2012 and June 2014 were reviewed for an association between anesthetic technique and intraoperative hemorrhage. Twenty patients received inhalational anesthetic agents, while 118 received intravenous anesthetics. Blood loss was estimated by the operating gynecologists. Results: The mean intraoperative blood loss for inhalational anesthetics (113.6 ml) was significantly higher than with noninhalational agents (40.2 ml) (p=0.007). Age, body mass index, and gestational age were not statistically different between the groups; the number of methylergonovine doses at induced abortion trended higher with inhalation anesthetics. Conclusions: The difference in blood loss between the two types of anesthetic techniques was statistically significant. These findings may be important for patients with significant anemia or at an increased risk of bleeding, such as those with unrecognized coagulopathies

An Analytical Study of Coupled Two-State Stochastic Resonators

The two-state model of stochastic resonance is extended to a chain of coupled two-state elements governed by the dynamics of Glauber's stochastic Ising model. Appropriate assumptions on the model parameters turn the chain into a prototype system of coupled stochastic resonators. In a weak-signal limit analytical expressions are derived for the spectral power amplification and the signal-to-noise ratio of a two-state element embedded into the chain. The effect of the coupling between the elements on both quantities is analysed and array-enhanced stochastic resonance is established for pure as well as noisy periodic signals. The coupling-induced improvement of the SNR compared to an uncoupled element is shown to be limited by a factor four which is only reached for vanishing input noise.Comment: 29 pages, 5 figure